scholarly journals Fibroblast Growth Factor Family in the Progression of Prostate Cancer

2019 ◽  
Vol 8 (2) ◽  
pp. 183 ◽  
Author(s):  
Jun Teishima ◽  
Tetsutaro Hayashi ◽  
Hirotaka Nagamatsu ◽  
Koichi Shoji ◽  
Hiroyuki Shikuma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Biological Function ◽  
Current Knowledge ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Tyrosine Kinase Signaling ◽  
Fibroblast Growth Factor Family ◽  
Development And Differentiation

Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) play an important role in the maintenance of tissue homeostasis and the development and differentiation of prostate tissue through epithelial-stromal interactions. Aberrations of this signaling are linked to the development and progression of prostate cancer (PCa). The FGF family includes two subfamilies, paracrine FGFs and endocrine FGFs. Paracrine FGFs directly bind the extracellular domain of FGFRs and act as a growth factor through the activation of tyrosine kinase signaling. Endocrine FGFs have a low affinity of heparin/heparan sulfate and are easy to circulate in serum. Their biological function is exerted as both a growth factor binding FGFRs with co-receptors and as an endocrine molecule. Many studies have demonstrated the significance of these FGFs and FGFRs in the development and progression of PCa. Herein, we discuss the current knowledge regarding the role of FGFs and FGFRs—including paracrine FGFs, endocrine FGFs, and FGFRs—in the development and progression of PCa, focusing on the representative molecules in each subfamily.

scholarly journals Role of Fibroblast Growth Factor 23 (FGF23) and αKlotho in Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Franz Ewendt ◽  
Martina Feger ◽  
Michael Föller
Keyword(s):  
Growth Factor ◽  
Life Span ◽  
Intracellular Signaling ◽  
Bone Cells ◽  
Current Knowledge ◽  
Transmembrane Protein ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Paracrine Effects

Together with fibroblast growth factors (FGFs) 19 and 21, FGF23 is an endocrine member of the family of FGFs. Mainly secreted by bone cells, FGF23 acts as a hormone on the kidney, stimulating phosphate excretion and suppressing formation of 1,25(OH)2D3, active vitamin D. These effects are dependent on transmembrane protein αKlotho, which enhances the binding affinity of FGF23 for FGF receptors (FGFR). Locally produced FGF23 in other tissues including liver or heart exerts further paracrine effects without involvement of αKlotho. Soluble Klotho (sKL) is an endocrine factor that is cleaved off of transmembrane Klotho or generated by alternative splicing and regulates membrane channels, transporters, and intracellular signaling including insulin growth factor 1 (IGF-1) and Wnt pathways, signaling cascades highly relevant for tumor progression. In mice, lack of FGF23 or αKlotho results in derangement of phosphate metabolism and a syndrome of rapid aging with abnormalities affecting most organs and a very short life span. Conversely, overexpression of anti-aging factor αKlotho results in a profound elongation of life span. Accumulating evidence suggests a major role of αKlotho as a tumor suppressor, at least in part by inhibiting IGF-1 and Wnt/β-catenin signaling. Hence, in many malignancies, higher αKlotho expression or activity is associated with a more favorable outcome. Moreover, also FGF23 and phosphate have been revealed to be factors relevant in cancer. FGF23 is particularly significant for those forms of cancer primarily affecting bone (e.g., multiple myeloma) or characterized by bone metastasis. This review summarizes the current knowledge of the significance of FGF23 and αKlotho for tumor cell signaling, biology, and clinically relevant parameters in different forms of cancer.

The role of the fibroblast growth factor family in bone‐related diseases

2019 ◽  
Vol 94 (4) ◽  
pp. 1740-1749 ◽  
Author(s):  
Jicheng Wang ◽  
Shizhang Liu ◽  
Jingyuan Li ◽  
Zhi Yi
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Family

Sequential roles for Fgf4, En1 and Fgf8 in specification and regionalisation of the midbrain

Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 945-959 ◽  
Author(s):  
H. Shamim ◽  
R. Mahmood ◽  
C. Logan ◽  
P. Doherty ◽  
A. Lumsden ◽  
...  
Keyword(s):  
Fibroblast Growth Factors ◽  
Retroviral Vector ◽  
Normal Function ◽  
Neural Plate ◽  
Avian Embryo ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Family ◽  
Expression Of Genes

Experiments involving tissue recombinations have implicated both early vertical and later planar signals in the specification and polarisation of the midbrain. Here we investigate the role of fibroblast growth factors in regulating these processes in the avian embryo. We show that Fgf4 is expressed in the notochord anterior to Hensen's node before transcripts for the earliest molecular marker of midbrain tissue in the avian embryo, En1, are detected. The presence of notochord is required for the expression of En1 in neural plate explants in vitro and FGF4 mimics this effect of notochord tissue. Subsequently, a second member of the fibroblast growth factor family, Fgf8, is expressed in the isthmus in a manner consistent with it providing a polarising signal for the developing midbrain. Using a retroviral vector to express En1 ectopically, we show that En1 can induce Fgf8 expression in midbrain and posterior diencephalon. Results of the introduction of FGF8 protein into the anterior midbrain or posterior diencephalon are consistent with it being at least part of the isthmic activity which can repolarise the former tissue and respecify the latter to a midbrain fate. However, the ability of FGF8 to induce expression of genes which have earlier onsets of expression than Fgf8 itself, namely En1 and Pax2, strongly suggests that the normal function of FGF8 is in maintaining patterns of gene expression in posterior midbrain. Finally, we provide evidence that FGF8 also provides mitogenic stimulation during avian midbrain development.

scholarly journals The role of fibroblast growth factors and their receptors in prostate cancer

2004 ◽  
Vol 11 (4) ◽  
pp. 709-724 ◽  
Author(s):  
B Kwabi-Addo ◽  
M Ozen ◽  
M Ittmann
Keyword(s):  
Prostate Cancer ◽  
Growth Factors ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Fgf Signaling ◽  
Prostate Cancer Progression ◽  
Fgf Receptor

Prostate cancer is the most common malignancy in men in the USA and the second leading cause of cancer deaths. Fibroblast growth factors (FGFs), including FGF1 (acidic FGF), FGF2 (basic FGF), FGF6 and FGF8 are all expressed at increased levels in prostate cancer as paracrine and/or autocrine growth factors for the prostate cancer cells. In addition, increased mobilization of FGFs from the extracellular matrix in cancer tissues can increase the availability of FGFs to cancer cells. Prostate cancer epithelial cells express all four types of FGF receptors (FGFR-1 to -4) at variable frequencies. Expression of FGFR-1 and FGFR-4 is most closely linked to prostate cancer progression, while the role of FGFR-2 remains controversial. Activation of FGF receptors can activate multiple signal transduction pathways including the phospholipase Cγ, phosphatidyl inositol 3-kinase, mitogen-activated protein kinase and signal transducers and activators of transcription (STAT) pathways, all of which play a role in prostate cancer progression. Sprouty proteins can negatively regulate FGF signal transduction, potentially limiting the impact of FGF signaling in prostate cancer, but in a significant fraction of prostate cancers there is decreased expression of Sprouty1 mRNA and protein. The effects of increased FGF receptor signaling are wide ranging and involve both the cancer cells and surrounding stroma, including the vasculature. The net result of increased FGF signaling includes enhanced proliferation, resistance to cell death, increased motility and invasiveness, increased angiogenesis, enhanced metastasis, resistance to chemotherapy and radiation and androgen independence, all of which can enhance tumor progression and clinical aggressiveness. For this reason, the FGF signaling system it is an attractive therapeutic target, particularly since therapies targeting FGF receptors and/or FGF signaling can affect both the tumor cells directly and tumor angiogenesis. A number of approaches that could target FGF receptors and/or FGF receptor signaling in prostate cancer are currently being developed.

scholarly journals Fibroblast growth factor 23 and its role in phosphate homeostasis

2010 ◽  
Vol 162 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Isolde Ramon ◽  
Pierre Kleynen ◽  
Jean-Jacques Body ◽  
Rafik Karmali
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Parathyroid Gland ◽  
Current Knowledge ◽  
Fibroblast Growth Factor 23 ◽  
Active Role ◽  
Feedback Loops ◽  
Fibroblast Growth ◽  
Phosphate Homeostasis

Phosphate homeostasis is complex and incompletely understood. The identification of different factors involved in the regulation of phosphate balance, also called phosphatonins, has largely changed our view on the regulation of phosphate homeostasis. The active role of bone has been demonstrated clearly. Currently, maintaining phosphate homeostasis is considered the result of a complex network of endocrine feedback loops between parathyroid gland, kidney, and bone. This review describes current knowledge on fibroblast growth factor 23, which is one of the best studied phosphatonins.

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